40(D-10) (+)-Lasonolide Aの全合成(口頭発表の部)

抄録

Lasonolide A (1) was isolated from an extract of the shallow water Caribbean marine sponge, Forcepia sp. by McConnell. This compound was discovered to inhibit the in vitro proliferation of A-549 human lung carcinoma cells as well as cell adhesion in a newly developed whole cell assay that detects signal transduction agents. Because of the intriguing structural features, for example the 20 membered polyene macrolide and the characteristic quaternary stereogenic center at C22, notable biological profiles and limited availability, lasonolide A represents an attractive target for total synthesis. Several synthetic attempts have been reported and to date two total syntheses have been communicated by Korean groups. In particular, Lee and co-workers revised the proposed structure and established the absolute configurations as shown in Figure 1. We report here the enantioselective total synthesis of the natural enantiomer (+)-lasonolide A employing a convergent strategy. Namely, the diastereoselectively synthesized three segments, the C1-C17, the C 18-C25 and the C26-C35 segments, were connected by sequential cross metathsis reaction, Yamaguchi's macrolactonization and Wittig reaction.